Glucose transporters in single skeletal muscle fibers. Relationship to hexokinase and regulation by contractile activity.

Glucose transport and phosphorylation are the first steps in the utilization of extracellular glucose by skeletal muscle. We have examined the relationships between proteins mediating these steps in single fibers of identified type dissected from rabbit skeletal muscle. The level of the glucose transporter isoform GLUT4, measured by immunoblotting, varied among fibers by a factor of 20 (slow oxidative > fast oxidative glycolytic > fast glycolytic). In fibers from the tibialis anterior muscle, GLUT4 was correlated (r2 = 0.75) with the activity of malate dehydrogenase, an enzyme representative of oxidative energy metabolism. In these fibers a strong correlation (r2 = 0.70) was also observed between GLUT4 and hexokinase activity. GLUT1 levels were barely detectable, regardless of fiber type. To investigate the possible role of muscle activity in controlling the expression of transporters, tibialis anterior muscles were activated by chronic electrical stimulation of the peroneal nerves. GLUT1 levels increased after 1 day of stimulation to a plateau that was severalfold higher than the level in non-stimulated cells. Hexokinase activity and the GLUT4 level changed in parallel: both were increased by approximately 2.5-fold after 1 day and by 14-fold after 21 days. Thus, while both GLUT1 and GLUT4 were regulated by muscle activity, only GLUT4 expression was coordinated with the expression of hexokinase.